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- W2413993846 startingPage "26" @default.
- W2413993846 abstract "Rho GTPases regulate cellular morphology and dynamics, and some are key drivers of cancer progression. This superfamily offers attractive potential targets for therapeutic intervention, with RhoA, Rac1 and Cdc42 being prime examples. The challenges in developing agents that act on these signaling enzymes include the lack of obvious druggable pockets and their membrane-bound activities. However, progress in targeting the similar Ras protein is illuminating new strategies for specifically inhibiting oncogenic GTPases. The structures of multiple signaling and regulatory states of Rho proteins have been determined, and the post-translational modifications including acylation and phosphorylation points have been mapped and their functional effects examined. The development of inhibitors to probe the significance of overexpression and mutational hyperactivation of these GTPases underscores their importance in cancer progression. The ability to integrate in silico, in vitro, and in vivo investigations of drug-like molecules indicates the growing tractability of GTPase systems for lead optimization. Although no Rho-targeted drug molecules have yet been clinically approved, this family is clearly showing increasing promise for the development of precision medicine and combination cancer therapies." @default.
- W2413993846 created "2016-06-24" @default.
- W2413993846 creator A5025099665 @default.
- W2413993846 creator A5079999468 @default.
- W2413993846 date "2016-06-13" @default.
- W2413993846 modified "2023-10-14" @default.
- W2413993846 title "Structural Mechanisms and Drug Discovery Prospects of Rho GTPases" @default.
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